Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: PTK2B

Gene summary for PTK2B

Gene summary.

Gene information	Species	Human
	Gene symbol	PTK2B
	Gene ID	2185
	Gene name	protein tyrosine kinase 2 beta
	Gene Alias	CADTK
	Cytomap	8p21.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q14289

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
2185	PTK2B	HTA11_2487_2000001011	Human	Colorectum	SER	8.25e-06	5.90e-01	-0.1808
2185	PTK2B	HTA11_347_2000001011	Human	Colorectum	AD	6.10e-16	6.59e-01	-0.1954
2185	PTK2B	HTA11_411_2000001011	Human	Colorectum	SER	1.25e-02	9.86e-01	-0.2602
2185	PTK2B	HTA11_696_2000001011	Human	Colorectum	AD	5.38e-07	5.24e-01	-0.1464
2185	PTK2B	HTA11_5212_2000001011	Human	Colorectum	AD	1.58e-08	6.99e-01	-0.2061
2185	PTK2B	A002-C-010	Human	Colorectum	FAP	2.35e-02	-1.14e-01	0.242
2185	PTK2B	A015-C-203	Human	Colorectum	FAP	1.71e-12	-2.25e-01	-0.1294
2185	PTK2B	A002-C-201	Human	Colorectum	FAP	2.31e-07	-2.72e-01	0.0324
2185	PTK2B	A001-C-108	Human	Colorectum	FAP	2.83e-06	-1.79e-01	-0.0272
2185	PTK2B	A002-C-205	Human	Colorectum	FAP	4.14e-09	-2.83e-01	-0.1236
2185	PTK2B	A015-C-006	Human	Colorectum	FAP	1.68e-06	-3.26e-01	-0.0994
2185	PTK2B	A015-C-106	Human	Colorectum	FAP	7.52e-05	-1.92e-01	-0.0511
2185	PTK2B	A002-C-114	Human	Colorectum	FAP	2.54e-05	-1.66e-01	-0.1561
2185	PTK2B	A015-C-104	Human	Colorectum	FAP	4.67e-14	-2.76e-01	-0.1899
2185	PTK2B	A001-C-014	Human	Colorectum	FAP	1.78e-05	-1.58e-01	0.0135
2185	PTK2B	A002-C-016	Human	Colorectum	FAP	4.31e-08	-2.27e-01	0.0521
2185	PTK2B	A015-C-002	Human	Colorectum	FAP	1.16e-03	-2.64e-01	-0.0763
2185	PTK2B	A001-C-203	Human	Colorectum	FAP	4.27e-03	-1.87e-01	-0.0481
2185	PTK2B	A002-C-116	Human	Colorectum	FAP	6.16e-10	-2.26e-01	-0.0452
2185	PTK2B	A014-C-008	Human	Colorectum	FAP	3.49e-04	-2.56e-01	-0.191

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:003030711	Liver	HCC	positive regulation of cell growth	88/7958	166/18723	3.95e-03	1.74e-02	88
GO:003153212	Liver	HCC	actin cytoskeleton reorganization	59/7958	107/18723	5.57e-03	2.32e-02	59
GO:00321471	Liver	HCC	activation of protein kinase activity	72/7958	134/18723	5.61e-03	2.33e-02	72
GO:00432791	Liver	HCC	response to alkaloid	62/7958	115/18723	8.79e-03	3.42e-02	62
GO:007135611	Liver	HCC	cellular response to tumor necrosis factor	115/7958	229/18723	1.08e-02	3.99e-02	115
GO:00420631	Liver	HCC	gliogenesis	148/7958	301/18723	1.10e-02	4.07e-02	148
GO:00454712	Liver	HCC	response to ethanol	72/7958	137/18723	1.10e-02	4.07e-02	72
GO:190440712	Liver	HCC	positive regulation of nitric oxide metabolic process	25/7958	41/18723	1.31e-02	4.69e-02	25
GO:000166721	Liver	HCC	ameboidal-type cell migration	226/7958	475/18723	1.35e-02	4.81e-02	226
GO:004592711	Liver	HCC	positive regulation of growth	128/7958	259/18723	1.41e-02	4.99e-02	128
GO:000989620	Oral cavity	OSCC	positive regulation of catabolic process	307/7305	492/18723	2.29e-26	7.64e-24	307
GO:003133120	Oral cavity	OSCC	positive regulation of cellular catabolic process	273/7305	427/18723	6.39e-26	2.02e-23	273
GO:004217620	Oral cavity	OSCC	regulation of protein catabolic process	254/7305	391/18723	1.07e-25	3.22e-23	254
GO:004586220	Oral cavity	OSCC	positive regulation of proteolysis	236/7305	372/18723	6.53e-22	1.38e-19	236
GO:000697920	Oral cavity	OSCC	response to oxidative stress	273/7305	446/18723	8.35e-22	1.65e-19	273
GO:190336220	Oral cavity	OSCC	regulation of cellular protein catabolic process	174/7305	255/18723	2.04e-21	3.70e-19	174
GO:190305020	Oral cavity	OSCC	regulation of proteolysis involved in cellular protein catabolic process	152/7305	221/18723	2.16e-19	3.15e-17	152
GO:004325420	Oral cavity	OSCC	regulation of protein-containing complex assembly	255/7305	428/18723	2.94e-18	3.15e-16	255
GO:000641720	Oral cavity	OSCC	regulation of translation	274/7305	468/18723	4.39e-18	4.63e-16	274
GO:200005820	Oral cavity	OSCC	regulation of ubiquitin-dependent protein catabolic process	118/7305	164/18723	9.37e-18	9.27e-16	118

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05135	Colorectum	AD	Yersinia infection	58/2092	137/8465	3.90e-06	4.35e-05	2.78e-05	58
hsa05170	Colorectum	AD	Human immunodeficiency virus 1 infection	72/2092	212/8465	1.40e-03	8.46e-03	5.39e-03	72
hsa05163	Colorectum	AD	Human cytomegalovirus infection	75/2092	225/8465	2.00e-03	1.10e-02	7.01e-03	75
hsa051351	Colorectum	AD	Yersinia infection	58/2092	137/8465	3.90e-06	4.35e-05	2.78e-05	58
hsa051701	Colorectum	AD	Human immunodeficiency virus 1 infection	72/2092	212/8465	1.40e-03	8.46e-03	5.39e-03	72
hsa051631	Colorectum	AD	Human cytomegalovirus infection	75/2092	225/8465	2.00e-03	1.10e-02	7.01e-03	75
hsa051352	Colorectum	SER	Yersinia infection	43/1580	137/8465	2.15e-04	2.10e-03	1.52e-03	43
hsa046702	Colorectum	SER	Leukocyte transendothelial migration	37/1580	114/8465	2.77e-04	2.56e-03	1.86e-03	37
hsa051702	Colorectum	SER	Human immunodeficiency virus 1 infection	58/1580	212/8465	1.08e-03	8.56e-03	6.21e-03	58
hsa051632	Colorectum	SER	Human cytomegalovirus infection	57/1580	225/8465	7.40e-03	3.84e-02	2.79e-02	57
hsa049122	Colorectum	SER	GnRH signaling pathway	27/1580	93/8465	9.68e-03	4.72e-02	3.43e-02	27
hsa051353	Colorectum	SER	Yersinia infection	43/1580	137/8465	2.15e-04	2.10e-03	1.52e-03	43
hsa046703	Colorectum	SER	Leukocyte transendothelial migration	37/1580	114/8465	2.77e-04	2.56e-03	1.86e-03	37
hsa051703	Colorectum	SER	Human immunodeficiency virus 1 infection	58/1580	212/8465	1.08e-03	8.56e-03	6.21e-03	58
hsa051633	Colorectum	SER	Human cytomegalovirus infection	57/1580	225/8465	7.40e-03	3.84e-02	2.79e-02	57
hsa049123	Colorectum	SER	GnRH signaling pathway	27/1580	93/8465	9.68e-03	4.72e-02	3.43e-02	27
hsa051356	Colorectum	FAP	Yersinia infection	43/1404	137/8465	1.21e-05	1.62e-04	9.86e-05	43
hsa046706	Colorectum	FAP	Leukocyte transendothelial migration	37/1404	114/8465	2.12e-05	2.53e-04	1.54e-04	37
hsa049126	Colorectum	FAP	GnRH signaling pathway	28/1404	93/8465	8.16e-04	5.14e-03	3.13e-03	28
hsa051636	Colorectum	FAP	Human cytomegalovirus infection	55/1404	225/8465	1.42e-03	7.67e-03	4.67e-03	55

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

PTK2B

SNV

Missense_Mutation

c.2871N>A

p.Met957Ile

p.M957I

Q14289

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A2-A0T2-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

xeloda

PTK2B

SNV

Missense_Mutation

rs750561555

c.553N>T

p.Arg185Trp

p.R185W

Q14289

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A2-A3XS-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

PTK2B

SNV

Missense_Mutation

c.973N>C

p.Glu325Gln

p.E325Q

Q14289

protein_coding

tolerated(0.24)

benign(0.044)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PTK2B

SNV

Missense_Mutation

c.1817G>T

p.Ser606Ile

p.S606I

Q14289

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PTK2B

SNV

Missense_Mutation

c.1681N>C

p.Glu561Gln

p.E561Q

Q14289

protein_coding

tolerated(0.06)

benign(0.006)

TCGA-C8-A12T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PTK2B

insertion

In_Frame_Ins

novel

c.2331_2332insCGGTGTCCCATGGTCCTATATTTGTTCTCAAGGAAATGCCTG

p.His777_Ser778insArgCysProMetValLeuTyrLeuPheSerArgLysCysLeu

p.H777_S778insRCPMVLYLFSRKCL

Q14289

protein_coding

TCGA-B6-A0RG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PTK2B

insertion

Frame_Shift_Ins

novel

c.789_790insGTCATAGATC

p.Thr264ValfsTer8

p.T264Vfs*8

Q14289

protein_coding

TCGA-BH-A0H7-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

PTK2B

insertion

Frame_Shift_Ins

novel

c.2148_2148+1insGTAAGCCAAGCCATGT

p.Pro717ValfsTer10

p.P717Vfs*10

Q14289

protein_coding

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

PTK2B

SNV

Missense_Mutation

novel

c.1757G>A

p.Arg586His

p.R586H

Q14289

protein_coding

deleterious(0)

possibly_damaging(0.854)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PTK2B

SNV

Missense_Mutation

rs773709584

c.2779N>A

p.Leu927Ile

p.L927I

Q14289

protein_coding

tolerated(1)

benign(0)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID	Symbol	Category	Interaction Types	Drug Claim Name	Drug Name	PMIDs
2185	PTK2B	DRUGGABLE GENOME, KINASE, ION CHANNEL, G PROTEIN COUPLED RECEPTOR, TYROSINE KINASE, ENZYME		PMID27774822-Compound-Figure10Example1
2185	PTK2B	DRUGGABLE GENOME, KINASE, ION CHANNEL, G PROTEIN COUPLED RECEPTOR, TYROSINE KINASE, ENZYME		Imidazo[4,5-c]pyridine derivative 1
2185	PTK2B	DRUGGABLE GENOME, KINASE, ION CHANNEL, G PROTEIN COUPLED RECEPTOR, TYROSINE KINASE, ENZYME		Aminotriazolopyridine derivative 1
2185	PTK2B	DRUGGABLE GENOME, KINASE, ION CHANNEL, G PROTEIN COUPLED RECEPTOR, TYROSINE KINASE, ENZYME		CID 94381	CHEMBL374632
2185	PTK2B	DRUGGABLE GENOME, KINASE, ION CHANNEL, G PROTEIN COUPLED RECEPTOR, TYROSINE KINASE, ENZYME		HTS-05058	CHEMBL261692
2185	PTK2B	DRUGGABLE GENOME, KINASE, ION CHANNEL, G PROTEIN COUPLED RECEPTOR, TYROSINE KINASE, ENZYME		PMID27774824-Compound-Figure11Example1up
2185	PTK2B	DRUGGABLE GENOME, KINASE, ION CHANNEL, G PROTEIN COUPLED RECEPTOR, TYROSINE KINASE, ENZYME		TCMDC-125185	CHEMBL580819
2185	PTK2B	DRUGGABLE GENOME, KINASE, ION CHANNEL, G PROTEIN COUPLED RECEPTOR, TYROSINE KINASE, ENZYME	inhibitor	CHEMBL3137331	DEFACTINIB
2185	PTK2B	DRUGGABLE GENOME, KINASE, ION CHANNEL, G PROTEIN COUPLED RECEPTOR, TYROSINE KINASE, ENZYME		PF-04965842	ABROCITINIB
2185	PTK2B	DRUGGABLE GENOME, KINASE, ION CHANNEL, G PROTEIN COUPLED RECEPTOR, TYROSINE KINASE, ENZYME		ASP-015K	PEFICITINIB

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